基于TCGA数据库分析ASPM在肺腺癌中的表达及临床意义

目的：探讨异常纺锤体样小头畸形相关基因（ASPM）在肺腺癌中的表达水平，及其与患者临床病理指标和预后的关系。方法：从癌症基因组图谱（TCGA）数据库下载肺腺癌组织和癌旁组织mRNA表达水平和临床病例资料，比较ASPM mRNA在癌组织和癌旁组织中的表达差异，统计学分析ASPM表达水平与肺腺癌患者临床病理指标及预后关系。通过R语言ballgown和ggplot包筛选高低表达ASPM组间差异基因并绘制火山图；利用DAVID工具对差异基因进行GO分析，采用GSEA预测ASPM可能调控的信号通路；STRING和Cytoscape分析关键基因及差异表达基因间的相互作用。结果：ASPM mRNA在肺腺癌中表达水平显著高于癌旁组织（P < 0.05）；ASPM表达水平与生存期相关，高表达ASPM肺腺癌患者预后较差（P < 0.05），是肺腺癌患者预后的独立危险因素，R语言ballgown包筛选出ASPM高低表达组间的差异表达基因共183个，差异表达基因富集到生物过程（BP）、细胞组分（CC）、分子功能（MF）在3个类别共19个亚类和18条KEGG通路；Cytoscape软件发现4个枢纽蛋白。结论：ASPM mRNA在肺腺癌患者中呈高表达且高表达组预后差，可作为判断肺腺癌预后的标志物。     

New evidence supporting lung cancer screening with low dose CT & surgical implications

IntroductionLung cancer is the leading cause of cancer-death worldwide. The U.S. Preventative Services Task Force (USPTSF) approved screening for current or former smokers aged 55–80 based on the results of the National Lung Screening trial (NLST). Following the NLST, new evidence has emerged from clinical trials and updates to previous trials prior to the anticipated update to the USPSTF guideline. We review the new evidence on lung cancer screening with low dose computed tomography (LDCT) and the surgical implications.MethodsA review of new literature was performed pertaining to lung cancer screening since implementation of UPSTF guidelines. Articles for inclusion were identified by both authors’, then search of the Pubmed and Cochrane database was performed from January 1st, 2013 through February 4th, 2020 using the MeSH search terms: “lung cancer”; “screening”; “low dose CT”. The results of these studies are summarized.ResultsWe identified multiple prospective randomized control trials and meta-analysis since the NLST supporting lung cancer-specific mortality with screening. We identified new nodule classification systems and the development of risk-models which may reduce false positive rates and identify high risk patients not currently eligible for screening. Finally, we discussed the surgical implications of screening.ConclusionNew data supports NLST findings and show ongoing benefit to LDCT for lung cancer screening. Standardized LDCT screening classification has been shown to reduce harm and lower false positive rates. Further study is needed regarding use of risk-modeling. Screening will require an increase in the thoracic workforce to accommodate the amount of surgically operable cancers.     

经筋刺法联合艾灸治疗阳虚型肺癌患者癌性疼痛的临床研究

目的观察经筋刺法联合艾灸治疗阳虚型肺癌患者癌性疼痛的临床疗效。方法将60例中晚期肺癌患者随机分为对照组和治疗组,每组30例。对照组予以三阶梯止痛治疗,治疗组在对照组基础上,予以经筋刺法联合艾灸治疗。两组均以4周为1个治疗周期,观察治疗后两组患者疼痛控制情况、生存质量,并对安全性进行评估。结果与治疗前相比,治疗后两组患者疼痛数字评价量表评分均呈现进行性的下降(P <0. 05)、阳虚证评分均有下降(P <0. 05)、生活质量评分各指标均有上升(P <0. 05);经治疗,治疗组与对照组相比,在疼痛数字评价量表评分、阳虚证评分以及生活质量评分等方面均有显著改善(P <0. 05)。结论经筋刺法联合艾灸能够在一定程度上缓解阳虚型肺癌患者癌性疼痛,并在改善患者阳虚症状以及生存质量方面具有积极作用。     

全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响

目的探讨全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响。方法收集接受肺癌根治术的84例患者的病历资料,按照患者所行麻醉方式的不同对其进行分组,单纯行全麻者42例归为对照组,行全麻复合硬膜外麻醉者42例纳入观察组,分析不同麻醉方式对患者外周血T细胞亚群及NK细胞活性影响的差异性。结果术后24 h观察组与对照组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、NK细胞水平均较术前明显降低,且术后24 h相比对照组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、NK细胞水平,观察组患者以上指标水平明显更高(P<0.05)。术后1周2组患者的CD3^+、CD4^+、CD8^+、CD4^+/CD8^+水平与术前相比并无明显差异(P>0.05),但NK细胞水平较术前明显降低(P<0.05),且术后1周相比对照组患者,观察组患者的NK细胞水平更高(P<0.05)。观察组患者的术后苏醒时间、术后拔管时间、自主呼吸恢复时间均明显短于对照组患者,2组差异有统计学意义(P<0.05)。结论相比单纯全麻,全麻复合硬膜外麻醉对肺癌根治术患者外周血T细胞亚群及NK细胞活性的影响更小,有助于患者术后的恢复。     

Spatial and Temporal Heterogeneity of Panel-Based Tumor Mutational Burden in Pulmonary Adenocarcinoma: Separating Biology From Technical Artifacts

BackgroundTumor mutational burden (TMB) is an emerging biomarker used to identify patients who are more likely to benefit from immuno-oncology therapy. Aside from various unsettled technical aspects, biological variables such as tumor cell content and intratumor heterogeneity may play an important role in determining TMB.MethodsTMB estimates were determined applying the TruSight Oncology 500 targeted sequencing panel. Spatial and temporal heterogeneity was analyzed by multiregion sequencing (two to six samples) of 24 pulmonary adenocarcinomas and by sequencing a set of matched primary tumors, locoregional lymph node metastases, and distant metastases in five patients.ResultsOn average, a coding region of 1.28 Mbp was covered with a mean read depth of 609x. Manual validation of the mutation-calls confirmed a good performance, but revealed noticeable misclassification during germline filtering. Different regions within a tumor showed considerable spatial TMB variance in 30% (7 of 24) of the cases (maximum difference, 14.13 mut/Mbp). Lymph node–derived TMB was significantly lower (p = 0.016). In 13 cases, distinct mutational profiles were exclusive to different regions of a tumor, leading to higher values for simulated aggregated TMB. Combined, intratumor heterogeneity and the aggregated TMB could result in divergent TMB designation in 17% of the analyzed patients. TMB variation between primary tumor and distant metastases existed but was not profound.ConclusionsOur data show that, in addition to technical aspects such as germline filtering, the tumor content and spatially divergent mutational profiles within a tumor are relevant factors influencing TMB estimation, revealing limitations of single-sample–based TMB estimations in a clinical context.     

肺癌围手术期免疫功能保护的研究进展

肺癌患者的细胞免疫、体液免疫、红细胞免疫等状况较正常人均存在着不同程度的低下。目前早中期患者肺癌的首选治疗方式仍然是手术切除治疗。虽然切除肿瘤可以逐渐消除瘤体本身造成的免疫抑制，但手术创伤引发的机体应激反应、神经内分泌变化、疼痛的刺激以及麻醉药物的使用在术后一段时间内反而会加重免疫抑制。因此针对围术期内多个治疗环节加以改进，可以有助于患者术后免疫功能的恢复，减少肿瘤复发、转移的几率。具体措施包括术前给予参芪扶正注射液、番茄红素、胸腺肽等药物以及预先给予适当的心理疏导以提升免疫力；术中更多的运用微创胸腔镜技术并在全身麻醉时联用硬膜外麻醉；围术期采用多模式联合镇痛，术前给予氟比洛芬酯等非甾体类抗炎药物开展超前镇痛，术后给予静脉持续自控镇痛时辅用地佐辛等药物或与肋间神经阻滞相结合，或改用硬膜外自控镇痛、自控椎旁神经阻滞等方法镇痛；此外术后建议给予患者早期营养支持，尽量减少不必要的输血，需要输血时使用辐照成分输血。     

CIP2A在子宫内膜样腺癌中的表达及临床意义

目的:探究蛋白磷酸酶2A(CIP2A)在子宫内膜样腺癌中的表达情况及临床意义。方法:选取2011年1月至2014年3月行手术切除并经病理证实的50例子宫内膜样腺癌(EAC)及同期行门诊刮宫术获取的40例正常增生期子宫内膜(NE)组织标本。应用RT-PCR、Western blot法检测EAC和NE组织中CIP2A mRNA及蛋白水平，免疫组化法检测CIP2A阳性表达情况。分析CIP2A在EAC和NE组织中的表达差异及与子宫内膜样腺癌临床病理特征的关系。采用Kaplan-Meier法分析CIP2A不同表达水平对患者预后生存的影响，通过COX分析预后独立危险因素。结果:免疫组化染色显示:CIP2A在子宫内膜样腺癌中呈高表达，阳性着色定位于细胞浆和细胞核中，EAC组织中CIP2A阳性表达率显著高于NE组织(P＜0.01)。RT-PCR和Western blot检测显示EAC组织中CIP2A mRNA及蛋白表达水平高于NE组织(P＜0.01)。CIP2A表达与EAC的组织学分级、FIGO分期、宫颈管受累情况、p53表达及Ki-67增殖指数有关（P＜0.05）。Kaplan-Meier法生存分析显示EAC患者5年无病生存率为92.0%、总生存率为88.0%；CIP2A表达、组织学分级、FIGO分期、肌层浸润深度、附件转移、脉管内癌栓及Ki-67增殖指数与患者预后不良相关（P＜0.05）。多因素分析显示，组织学分级、FIGO分期及脉管内癌栓是影响子宫内膜样腺癌患者预后生存的独立危险因素（P＜0.05）。结论:CIP2A在子宫内膜样腺癌中呈高表达，与患者总生存率下降相关，并非影响患者预后的独立危险因素。     

Stereotactic Body Radiotherapy for Centrally Located Primary Non–Small-Cell Lung Cancer: A Meta-Analysis

BackgroundThe purpose of the study was to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for centrally located, primary non–small-cell lung cancer (NSCLC).Materials and MethodsSystematic search of 4 databases (PubMed, MEDLINE, EMBASE, and Cochrane Library) was performed for literature published until May 9, 2018. Primary (overall survival [OS] and local control [LC] rates) and secondary (Grade ≥3 toxicity) endpoints were reported.ResultsThirteen studies encompassing 599 patients with central NSCLCs were included. Median values of T1 tumor proportion, tumor size, and median survival were 55.3% (range, 0%-75%), 3.3 (range, 2.1-4.1) cm, and 26 (range, 14-68.9) months, respectively. Pooled rates of 1-, 2-, and 3-year OS rates were 84.3% (95% confidence interval [CI], 75.7-90.3), 64.0% (95% CI, 52.9-72.2), and 50.5% (95% CI, 39.4-61.5), respectively. Pooled rates of 1-, 2-, and 3-year LC rates were 89.4% (95% CI, 80.8-94.4), 82.2% (95% CI, 71.7-89.4), and 72.2% (95% CI, 55.0-84.7), respectively. Pooled rate of Grade ≥3 complication was 12.0% (95% CI, 7.3-19.0). Meta-regression analyses showed significant positive relationships between biologically equivalent dose using an α/β of 10 Gy in the linear quadratic model (BED_10Gy) and 1- and 2-year LC rates (P < .001 and P < .001), and 1- and 2-year OS rates (P = .0178 and P = .032), and Grade ≥3 complication rate (P = .0029). In subgroup comparisons between BED_10Gy <100 Gy versus ≥100 Gy, 1- and 2-year LC rates were significantly different but not for OS and Grade ≥3 complication rates.ConclusionOur results suggests that SBRT is potent for tumor control in central NSCLC, although complications should be further minimized through optimization of dose-fractionation scheme and accurate planning. Using BED_10Gy ≥100 Gy yielded higher LC rates, and dose escalation was related to OS, LC, and complications.